The present invention relates to the site-specific delivery of therapeutic agents to target locations within body cavities, vasculatures, or tissues.
The treatment of disease such as vascular disease by local pharmacotherapy presents a means of delivering therapeutic drug doses to target tissues while minimizing systemic side effects. Recently, for example, the local delivery of gene constructs to effect vascular response has gained increased interest. Gene transfection of vascular smooth muscle cells in vivo, however, remains a problem due to low transfer efficiency attributed in part to inefficient local delivery devices and to the barrier properties of the vessel wall.
As an example of localized delivery of therapeutic agents, in vivo adenoviral gene transfer has been accomplished with the use of site-specific delivery catheters. Independent of the local delivery device used, most studies have delivered viral doses ranging from 1xc3x97109 to 1xc3x971010 pfu/ml over extended delivery times of 20 minutes or longer, and typically in delivery volumes of 1 ml or more. Although these conditions are widely used, the lack of optimization studies with local delivery devices suggests that delivery conditions are not necessarily optimal. Moreover, conventional localized techniques are often invasive in that they typically involve side branch ligation, long delivery times, and when the delivery device is an expandable device such as a balloon catheter, these techniques usually are associated with high pressures to accomplish drug delivery. Localized delivery techniques making use of long delivery times and high pressures and volumes often result in tissue damage, ischemia and other problems. Attempts have been made to reduce the delivery time from an infusion based device using a polymer carrier such as Poloxamer (BASF Corporation), whereby delivery times are reduced from 30 minutes to 5 minutes. The clinical utility of this approach, however, remains uncertain.
In one aspect, the present invention includes a method of site-specifically delivering a therapeutic agent to a target location within a body cavity, vasculature or tissue. The method comprises the steps of providing a medical device having a substantially saturated solution of therapeutic agent associated therewith; introducing the medical device into the body cavity, vasculature or tissue; releasing a volume of the solution of therapeutic agent from the medical device at the target location at a pressure of from about 0 to about 5 atmospheres for a time of up to about 5 minutes; and withdrawing the medical device from the body cavity, vasculature or tissue.
In another aspect, the present invention includes a system for delivering a therapeutic agent to a body cavity, vasculature or tissue, comprising a medical device having a substantially saturated solution of the therapeutic agent associated therewith.